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The minimum exposure to estrogen required to cause estrogen-withdrawal migraine has been studied by giving long-acting estradiol valerate to four women and short-acting estradiol benzoate to two women. It was found that several days of exposure to high estrogen levels were needed to cause migraine on estrogen withdrawal. Oral administration of estrogen supplements in the form of estradiol valerate or as conjugated equine estrogens during the premenstrual phase in four women did not significantly affect plasma levels of estradiol, nor was it effective in preventing menstrual migraine.

Prophylaxis of menstrual migraine was attempted in five women, using estradiol implants. The treatment was successful in suppressing ovulation and in producing high, although fluctuating, levels of estradiol in the plasma. Clinically this was associated with severe menstrual disturbance. The regular periodicity of the headaches was lost, but clinical benefit was unpredictable, with some patients actually experiencing more headaches than before the treatment. The administration of progesterone against a background of prolonged exposure to high estrogen levels did not provoke migraine, nor in any case did its subsequent withdrawal result in migraine. These findings cast further doubt on the importance of progesterone withdrawal in the etiology of menstrual migraine.

As Critcheley and Ferguson 1 said before the Harveian Society, "Migraine has been the happy hunting ground of the theorist, and the problem has been attacked by representatives of all branches of medicine. Each in turn has discovered in migraine phenomena pertaining to his own specialty... has hit upon the true nature of the malady... has found the infallible remedy. Obviously, such mutually exclusive viewpoints cannot all be entirely correct, and the multiplicity and diversity of the hypotheses suggest that the problem is more complex than imagined, and probably one which presents a number of facets." It is my purpose in this paper, which records the results of a hitherto unreported method of treatment, to shed more light on the nature of this puzzling malady and perhaps also to add something to our relatively meager knowledge of the gonadotropic factor extracted from pregnancy urine. 2 However, it must be kept